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Synthesis and Characterization of an RNA Dinucleotide Containing a 3‘- S -Phosphorothiolate Linkage

1996; American Chemical Society; Volume: 118; Issue: 43 Linguagem: Inglês

10.1021/ja9616903

1943-2984

Lara B. Weinstein, David Earnshaw, Richard Cosstick, Thomas R. Cech,

Metal complexes synthesis and properties

The synthesis of an RNA dinucleotide (IspU) containing a 3'-S-phosphorothiolate linkage is described. The compound is prepared from 9-(3-deoxy-3-iodo-β-d-xylofuranosyl)hypoxanthine with installation of the phosphorothiolate group via an Arbusov reaction and protection of the ribose 2'-hydroxyl as a silyl ether. IspU is found to be a substrate for several enzymes including T4 polynucleotide kinase, snake venom phosphodiesterase, and ribonuclease T2. Base-catalyzed cleavage of the dinucleotide is accelerated (∼2000-fold) relative to that of the phosphate-linked compound IpU. Product characterization and kinetic analysis show that IspU is cleaved through the same mechanism as IpU. The observed rate acceleration is argued to reflect stabilization of the anionic transition state by the polarizable sulfur atom.